Abstract

The Regulation and approval process of medical devices are different from regulation and approval process of medicinal products. For instance, in the US, medical devices are regulated by the FDA branch called the center for devices and radiological health (CDRH). Some of the differences in approach employed in evaluating medical devices depends on the functionality, utility and effectiveness. For example, in the medicinal product’s phase 1 clinical trials, researcher’s objective accesses tolerable dose for an investigational medicinal product. Contrary to device evaluation, dosage assessment is not a possible option with a clinical trial involving an investigational medical device. Rather, the evaluation research for medical devices depend on whether the device performance meets the stated claim of the device utility and function. Moreover, the level of risks and evaluation temerity of a medical device assessment depends on the class of the device. Medical devices are classified into three classes; class I, class II and class III.

Regulation of Medical Devices

In the US, the medical device approval process is under the purview of the CDRH branch of the FDA. Before any medical device is approved or rejected by the CDRH, it must go through a review and validation process. In some cases, an investigational clinical trial for a class III device is unavoidable. The clinical trial process may be stringent, and premarket approval (PMA) may be required depending on the class of the medical device and level of risks involved. In the US, the medical device approval process and marketing regulations are under the section 510 (k) of the food, drug and cosmetic (FD & C) Acts of 1976 (NG, 2009). Before and after 1976, any medical device in use, which has not gone through the FD & C process were considered pre-amendment devices (Whitmore, 2004). It took the CDRH several years to classify all pre-amendment devices in the US, and currently, all pre-amendment devices have been classified by the FDA.

Device manufacturers intending to release a medical device in the market must register and notify the regulatory agency within the jurisdiction of the marketing targets, at least 90 days in advance. This notification process is called “Premarket Notification” (PMN) or 510(k). This notification will allow the regulatory agency to determine the class of the device. Perhaps, any device that is released in the market through a 510(k) notification must be “substantially equivalent” to a device already on the market. Prior to May 28th, 1976, a “predicate device,” released in the market through the 510(k) process is technically not “approved” by the FDA. However, they are referred to as “cleared” or “510(k) cleared” devices and can be marketed and sold in the US. On the other hand, if the device is significantly different in terms of design, energy source, material, manufacturing process, chemical composition, or on intended utility relative to a pre-1976 device, then the device must go through the PMA process (Whitmore, 2004).

A class I medical device poses minimal potential harm to users. These types of devices do not require premarket approval or clearance but must follow general controls. General control is the minimum requirement for a class I medical device and about 55% of medical devices are classified under class I device (Whitmore, 2004). In addition, general control requires registration of the manufacturing location, all lists of marketed devices, cGMP information, labeling, etc. Moreover, a class I device is not intended for sustaining/supporting life and should not be an important device for preventing impairments to human life and should not pose a potential unreasonable risk of illness or injury (Whitmore, 2004). Some class I devices that has beencleared and currently in use includes dental floss, tongue depressors and examination gloves. Although, a class I device is exempt from premarket notification, however, the regulatory agency still remain subject to premarket notification requirements involving “reserved” class I devices such as “ammonia test system” or “surgeon gloves” (Whitmore, 2004).

The Class II medical device has higher risks than a class I device, and about 40 % of medical devices are classified under class II device. These types of devices are cleared for marketing purposes using the 510(k) process. It also has general and special control with/without exemption (Whitmore, 2004). Special control applies to class II devices because of the potential safety issue a class II may pose to users. In addition, class II devices require demonstration of equivalence with equal or better efficacy and safety to an approved device performing a similar function. However, the demonstration of equivalence does not usually involves an actual clinical trial; hence, the device approval process is considered a “regulatory-cleared” device in contrast to an “approved” device (Lyman, n.d). More importantly, a class II device follows the regulatory agency’s mandatory standards, regulatory guidance and post market surveillance (Whitmore, 2004). Moreover, the “predicate device” is often used to clear devices for marketing purposes, a device which do not meet the criteria to be considered a class III device. Some examples of Class II devices includes diagnostic tests, cardiac catheters, amalgam alloys, verichips and hearing aids.

On the other hand, Class III devices pose the highest potential risk or harm to users. Among all medical devices cleared or approved by the CDRH in the US, 5% of the devices are under a class III category (Whitmore, 2004). The major differences between a class III device and the other two classes of medical devices (class I and class II) involves higher potential risk with class III device, and premarket approval (PMA) is required for a class III medical device (Whitmore, 2004). The PMA is required for class III devices mostly due to insufficient information to assure safety and effectiveness through general or special control assessment. Thus, any class III device requires a PMA, and rigorous review similar to the NDA or BLA before the device is released in the market. Most importantly, a class III device requires a preclinical and interventional clinical trial to demonstrate reasonable assurance of the effectiveness and safety of the device (Lyman, n.d). Therefore, any trial involving human subjects require an investigational device exemption (IDE), a process similar to an IND application. The safety and efficacious demonstration of a class III medical device is usually based on a single study with a strong scientific evidence indicating that the benefits outweigh the risks the device may pose (Lyman, n.d). Some examples of a class III device include devices that support and sustains life such as replacement heart valve, artificial heart (SynCardia), silicon gel for breast implant, and automated external defibrillator.

Clearly, there are some key differences between medicinal products and device development, approval and regulatory process. For instance, most medicinal products’ patents in pharmaceutical industries last for 20 years, but patents for medical devices only last for 14 years (VanHout & Whitmore, 2013). In some cases, medicinal product’s patent may be extended especially with orphan drugs. On the contrary, it is usually difficult to extend patent on medical devices. Furthermore, the medical device regulation improvement in most cases is 10 years behind drug regulations because medicinal pharmaceutical companies are more sophisticated in conducting research and development in medicinal products than in medical devices. Moreover, medicinal product’s regulatory process is more stringent than the device regulatory process.

References

Lyman, G. (n.d).What are the differences between approving and using new drugs and new devices in the United States? Retrieved from http://www.asco.org/ASCOv2/Department %20Content/IMedia/Educational%20Book/PDF%20Files/2012/BC/bcs00112000050.pdf.

NG. R. (2009). Drugs: From discovery to approval (2nd ed.). Hoboken, NJ: Wiley-Blackwell.

VanHout, W & Whitmore, E. (2013). Medical device development. Retrieved from https://class.waldenu.edu/webapps/portal/frameset.jsp?tab_tab_group_id=_2_1&url= %2Fwebapps%2Fblackboard%2Fexecute%2Flauncher%3Ftype%3DCourse%26id %3D_2099284_1%26url%3D.

Whitmore, E. (2004). Development of FDA-regulated medical products: Prescription drugs, biologics, and medical devices. Milwaukee, WI: ASQ Quality Press.